Porphyrin症

The Porphyrias

I．まえがき

　定義：Schultz^21）により1874年初めて記載されてすでに90年の歴史を持つporphyrin症は，遺伝性を有する代謝性疾患でいわゆるGarrod^22）の"inborn error ofmetabolism"の一つに数えられ，porphyrin体あるいはその前駆物質の体内蓄積・体外排泄増加による暗赤色尿を共通症状とし，ほかの疾患・薬剤などによる二次的porphyrin代謝異常（主として尿中coproporphyrinの増加）をきたす状態であるporphyrin尿症と区別されてさた。しかしトルコにおけるhexachlorobenzeneによるporphyrin症^{23）24）26）}，bantuporphyrin症^25），alcoholによるporphyrin症などは生化学的・臨床的に遺伝性を有するporphyrin症と区別つかず，最近では遺伝性・後天性を問わず臨床症状が直接porphyrin代謝異常に関係するものをporphyrin症とし，直接関係ないものをporphyrin尿症としている^1）5）。主なporphyrin尿症は第1表^5）のごとくである。以下porphyrinは単にPと省略記載する。

　This papar is the review of the diseases ofporphyrin metabolism and contains Ⅰ) Introduction (definition, history, classification, distribution, and incidence), Ⅱ) Normal porphyrinmetabolism, Ⅲ) Erythropoietic porphyria (congenital porphyria, erythropoietic protoporphyria, hereditary coproporphyria and coproporphyrinamische Lichtempfindlichkeit). IV) Acuteintermittent porphyria (introduction, clinicalfeatures, precipitating factors, clinical andlaboratory findings, pathology, pathogenesisand therapy), Ⅴ) Porphyria cutanea tarda, Ⅵ) Experimental porphyria and Ⅶ) Discussion and summary.

　Although great progress has been madeduring the last decade, the exact pathogenesis of the porphyrias still remains obscure.

　As a result of experimental studies on DDC(3,5-Dicarbethoxy-L4-Dihydrocollidine) porphyria, we put forwards the new hypothesis thatthe primary lesion in hepatic porphyrias isdue to the anoxia or aredoxia of the tissueswhich precipitates a positive feedback mechanism and induces the over-synthesis of a-aminolaevulinic acid (ALA) synthetase in theliver mitochondria, resulting in the overproduction of ALA and porphobilinogen PBG).

　We also showed the possibility that in hepatic porphyrias the appearance of neurological symptoms may be due to the severity ofanoxia and the different patterns of the excretion of porphyrins and its precursors invarious types of hepatic porphyrias may bedue to the degree of ALA synthetase induction and the capacity of PBG-ase activity.

　A biochemical studies on the surgically biopsied liver of a patient with acute intermittent porphyria showed ALA synthetase activity was markedly increased in porphyricliver mitochondria as compaired with controland ALA dehydrase activity was elevated toapproximately twice the control level, while PBG-ase and chelatase activity stayed nearlythe same and catalase activity was decreasedabout 40% in porphyric liver.

　These results strongly indicate that theoverproduction of the porphyrin precursors, resulting from the increased ALA synthetaseactivity and normal PBG-ase activity, alsooccurs in human porphyric liver and supportthe above hypothesis.